title: Polyhydroxybutyrate targets mammalian mitochondria and increases permeability of plasmalemmal and mitochondrial membranes.
abstract: Poly(3-hydroxybutyrate) (PHB) is a polyester of 3-hydroxybutyric acid (HB) that is ubiquitously present in all organisms. In higher eukaryotes PHB is found in the length of 10 to 100 HB units and can be present in free form as well as in association with proteins and inorganic polyphosphate. It has been proposed that PHB can mediate ion transport across lipid bilayer membranes. We investigated the ability of PHB to interact with living cells and isolated mitochondria and the effects of these interactions on membrane ion transport. We performed experiments using a fluorescein derivative of PHB (fluo-PHB). We found that fluo-PHB preferentially accumulated inside the mitochondria of HeLa cells. Accumulation of fluo-PHB induced mitochondrial membrane depolarization. This membrane depolarization was significantly delayed by the inhibitor of the mitochondrial permeability transition pore - Cyclosporin A. Further experiments using intact cells as well as isolated mitochondria confirmed that the effects of PHB directly linked to its ability to facilitate ion transport, including calcium, across the membranes. We conclude that PHB demonstrates ionophoretic properties in biological membranes and this effect is most profound in mitochondria due to the selective accumulation of the polymer in this organelle.
authors.affiliation: Department of Physiology and Biophysics, Dalhousie University, Halifax, Novia Scotia, Canada.
authors.forename: Pia A
authors.initials: PA
authors.lastname: Elustondo
authors.forename: Plamena R
authors.initials: PR
authors.lastname: Angelova
authors.forename: Michał
authors.initials: M
authors.lastname: Kawalec
authors.forename: Michał
authors.initials: M
authors.lastname: Michalak
authors.forename: Piotr
authors.initials: P
authors.lastname: Kurcok
authors.forename: Andrey Y
authors.initials: AY
authors.lastname: Abramov
authors.forename: Evgeny V
authors.initials: EV
authors.lastname: Pavlov
mesh_terms: D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D016572:Cyclosporine / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006885:Hydroxybutyrates / Q000494:pharmacology*; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051336:Mitochondrial Membranes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D000083162:Mitochondrial Permeability Transition Pore; D010539:Permeability / Q000187:drug effects*; D011091:Polyesters / Q000494:pharmacology*; D000091402:Prohibitins; D000094122:Polyhydroxybutyrates
chemical_list: D002118:Calcium; D016572:Cyclosporine; D006885:Hydroxybutyrates; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D011091:Polyesters; D000091402:Prohibitins; C000717328:PHB protein, human; C003182:poly-beta-hydroxybutyrate; D000094122:Polyhydroxybutyrates